Pharmacokinetic-pharmacodynamic modeling of daurisoline and dauricine in beagle dogs

Acta Pharmacol Sin. 2003 Oct;24(10):1011-5.

Abstract

Aim: To study the combined pharmacokinetic-pharmacodynamic (PK-PD) model of daurisoline and dauricine, and compare their effects on cardiac electrophsiology, blood pressure, and hemodynamics in beagle dogs.

Methods: The plasma drug concentration was determined by the reversed-phase HPLC method and the effects on cardiac and hemodynamics were recorded by polygraph. The pharmacokinetic and PK-PD model parameters were calculated.

Results: The pharmacokinetics were best fitted to a two-compartment open model, and the relationship between effect and effect compartment concentration of both drugs could be represented by the sigmoid-E(max) model. There were no significant differences in main pharmacokinetics and PK-PD parameters between the two drugs.

Conclusion: No statistically different kinetic disposition characteristics and potencies of inhibitory effects on myocardial function of daurisoline and dauricine were found in beagle dogs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids*
  • Animals
  • Anti-Arrhythmia Agents / isolation & purification
  • Anti-Arrhythmia Agents / pharmacokinetics*
  • Anti-Arrhythmia Agents / pharmacology
  • Area Under Curve
  • Benzylisoquinolines / isolation & purification
  • Benzylisoquinolines / pharmacokinetics*
  • Benzylisoquinolines / pharmacology
  • Blood Pressure / drug effects
  • Dogs
  • Electrocardiography / drug effects
  • Female
  • Heart Rate / drug effects
  • Male
  • Menispermum / chemistry
  • Plants, Medicinal / chemistry
  • Tetrahydroisoquinolines / isolation & purification
  • Tetrahydroisoquinolines / pharmacokinetics*
  • Tetrahydroisoquinolines / pharmacology

Substances

  • Alkaloids
  • Anti-Arrhythmia Agents
  • Benzylisoquinolines
  • Tetrahydroisoquinolines
  • daurisoline
  • dauricine